10 Synthetic Methods By P. A. CHALONER School of Chemistry and Molecular Sciences University of Sussex Brighton BNl 9QJ 1 Introduction Despite the arrival of a new reporter the format of this report remains essentially the same as that of the past few years with a broad division into two sections. The first details reactions in which new carbon-carbon bonds are made or broken and new carbon skeleta constructed and the second deals with functional group transfor- mations. The first section is further sub-divided according to the type of transforma- tion (coupling of separate fragments cyclization cycloaddition etc.) and the latter into oxidative reductive and non-redox conversions. As always such a review must be extremely selective and whilst every attempt has been made to include contributions of general interest and applicability the author expresses her regret that some valuable material must be excluded.2 C-C Connection and Disconnection Connection of Separate Fragments.-Enolutes and their Equivalents. Again this year enolates figure strongly in C-C bond-forming methodology and again stereoselec- tive reactions have proved among the most interesting. Enantioselective deproton- ation of ketones by a chiral lithium amide base such as (1) (R' = H alkyl or Ar; R2-R" = H or alkyl; X = H OMe or NR2) has been achieved for 4-alkyl- cyclohexanones trimethylsilyl enol ethers being formed with up to 98% enantiomer excess on quenching with Me,SiCl.' Similar results were found with 2,6-dialkyl- cyclohexanones.* Ultrasound has been used to accelerate the generation and C-ethoxythiocarbonylation of en~lates,~ and as later sections will reveal this technique has found many new applications this year.Alkylation of chiral amide enolates (Scheme 1) may be achieved in an extremely stereoselective manner the product being hydrolysed to give an asymmetrically R. Shirai M. Tanaka and K. Koga J. Am. Chem. SOC.,1986 108 543. N. S. Simpkins J. Chem. SOC. Chem. Commun. 1986 88. M. A. Palominos R. Rodriguez and J. C. Vega Chem. Left. 1986 1251. 241 I? A. Chaloner ,OMOM OMOM I,. II I 111 .. -. ... R.qN3 NCYN5 NC NC O< i.,-.';OM 0' <OMOM OL OMOM OMOM R' R2 x NC COOH 80-90% e.e. Reagents i BuLi THF; ii R'X; iii R'X; iv HCI H,O; v K2C0, MeOH Scheme 1 I-I Me vii R'R~CHCOOH Reagents i BuLi; ii R'X; iii BuLi; iv R'X; v MeI; vi R3M; vii H30+ Scheme 2 dialkylated 2-cyanoacetic acid.4 Successive lithiations and alkylations of the tetrahy- drofolate coenzyme model (2) also provided convenient syntheses of dialkylated acids and ketones (Scheme 2).5 Ally1 derivatives have been shown to react readily with enolate anions in the presence of palladium( 0) complexes the reaction proceeding via cationic 73-allyl palladium complexes.Two examples of this reaction have shown useful degrees of enantioselectivity. Racemic (3) reacted with the anion of pentane-2,4-dione in the presence of (4) to give (5) in 97% chemical and 90%S optical yield (Scheme 3). The presence of the -CH20H groups in the catalyst is crucial and their function is thought to be to coordinate the incoming nucleophile.6 The palladium-catalysed allylation of chiral enamines (6),prepared from a proline derivative occurred with 100% chirality transfer (Scheme 4>.7 T.Hanamoto T. Katsuki and M. Yamaguchi Tetrahedron Lett. 1986 27 2463. ' M. W. Anderson R. C. F. Jones and J. Saunders J. Chem. SOC. Perkin Trans. I 1986 205 and 1995. T. Hayashi A. Yamamoto T. Hagihara and Y. Ito Tetrahedron Lett. 1986 27 191, ' K. Hiroi K. Suya and S. Sato J. Chem. SOC.,Chem. Commun. 1986 469. Synthetic Methods Fe &PPh2 phPPh OCOMe CH (COMe)2 Reagents i Na[CH(COMe)2] [{( q3-C3H5)PdCI},] Scheme 3 3 . .. I II -Reagents i [Pd(PPh,),] CHCI,; ii H@ Scheme 4 ,OSiMe OMe Reagents i TMSOTf -78 "C; ii TiCI, -78 "C; iii PDC Scheme 5 Two particularly facile preparations of spirocyclic ketones have been reported.In the first a cycloalkanone enolate is generated using potassium t-butoxide and ultrasound and reacts in a one-pot process with a,w-dibromoalkanes. The method is versatile giving good to excellent yields for a range of ring sizes.' Scheme 5 shows an alternative strategy; the initial step involves reaction of the silyl enol ether with the acetal displacing one methoxy group. This is followed by attack of the alkyltin moiety on the aldehyde accelerated by a Lewis acid with oxidation to give the final product.' There has been continued progress and extensive interest in the area of diastereoselective aldol condensations.It was known that p-silyl enolates could be alkylated with high diastereoselectivity and control of three contiguous chiral centres 'T. Fujita S. Watanabe M. Sakamoto and H. Hashimoto Chem. Znd. (London) 1986 427. T. V. Lee K. A. Richardson and D. A. Taylor Tetrahedron Lett. 1986 27 5021. 244 P. A. Chaloner has now been achieved (Scheme 6) in the reaction of (7). The outcome of the aldol reaction depends on the geometry of the starting enolate which is readily controlled. The product was used in a stereospecific synthesis of ally1 silanes." The boron enolate formed in situ from 3-pentanone and BC13 reacted with benzaldehyde to give an aldol with 95% syn-stereoselectivity. Similar results were obtained using ROBC12 prepared in situ." One of the best diastereofacial selectivities reported this year (Scheme 7) involved the titanium enolate of (8) which gave (9) and (10) in the ratio of 99:l on reaction with propanal.12 SiMe2Ph R' SiMe2Ph PhMeu:Me -1 ,COOMe RZ R' + I (7) ..... II 111I SiMelPh & ,COOMe 1 R' ' + J. R2 'OH R From (7) A:B = 89:ll;from (7a) A:B = 6:94 Reagents i R2CH0 -78 "C; ii LNH4]C1; iii LDA THF; iv Me2NCH(OMe),; vi PhS02CI; vii collidine A Scheme 6 OSi Mez( C Me3) Me OSiMe2(CMe3) ".a"i; i,ii,iii ~tfl CY + OH (9) (8) Reagents i LDA THF; ii CITi(OCHMe2)3; iii EtCHO (4 equiv.) Scheme 7 lo I. Fleming and J. D. Kilburn J. Chem. SOC.,Chem. Commun. 1986 305; I. Fleming and A.K. Sarkar J. Chem. Soc. Chem. Commun. 1986 1199. " H.-F. Chow and D. Seebach Helu. Chim. Acto 1986 69 604. I* C. Siege1 and E. R. Thornton Tetrahedron Left.. 1986 27 457. Synthetic Methods One route to chiral aldol products involves the use of a chiral auxiliary as a temporary appendage to one partner in the reaction (Scheme 8). Thus chiral a-halogenoimide enolates react with aldehydes to give (11) as essentially the sole product. Removal of the auxiliary and cyclization gave a chiral epoxide.I3 In the related reaction of the tin enolate of a thiocyanate derivative the ultimate product was an optically pure 2-methylamino-3-hydroxy carboxylic acid (Scheme 9).14 N-Methylephedrine was the chosen auxiliary in the reaction of (12) (Scheme 10); anti :syn ratios in the product ranged from 10 1 to greater than 30 1 which was a considerable improvement over the analogous reaction in the absence of the titanium Reagents i Bu,B (Me,CH),NEt 0 "C; ii C,H,,CHO -78 "C; iii PhCH,OLi Scheme 8 OSnX NCS i ii /111 iv v vi vii NHMe Reagents i [Sn(OTf),]; ii RCHO; iii Mg[OMe] MeOH; iv [Me,O][BF,]; v H,O; vi KOH; vii H30+ Scheme 9 MezN4%.Me (12) Reagents RCHO TiCI, PR, CH,CI Scheme 10 l3 A. Abdel-Magid L. N. Pridgen D. S. Eggleston and I. Lantos J. Am. Chem. Soc. 1986 108 4595. D. A. Evans and A. E. Weber J. Am. Chem. Soc. 1986 108 6757. 246 P. A. Chaloner salt and phosphine. Enantiomer excesses in the hydrolysed product were up to 94% without purification of the intermediates but optically pure material was readily obtained by flash chromatography of the diastereoisomers before hydr~lysis.'~ The chiral boron enolate of 3-pentanone synthesized from (13) (iPC = isopinocampheyl) in the presence of base gave up to 82% enantiomer excess in a syn-product from its reaction with acetaldehyde.16 n A,,B(iPC)OTf (13) An alternative approach to enantioselective aldol reactions involved the use of a chiral Lewis acid such as (14) as catalyst; in its presence 3,3-dimethyl-2-butanone reacted with 2,2-dimethylpropanal to give (15) in 84% enantiomer excess.l' The chiral base (16) was used in the reaction of a tin(Ir) thioester enolate with an aldehyde in optical yields varying from 55 to 80%.18 Such thioester enolates prepared by the addition of a tin(I1) thiolate to a ketene also reacted readily with aldimines (17) to give 3-alkylamino thioester derivatives with high anti :syn ratios (Scheme 11 ).19 RH rHphz (17) Reagents i [Sn(SCMe,)2] THF -78 "C; ii [Sn(OTf),]; iii (17) Scheme 11 Two new practical syntheses of Reformatsky reagents have been described (Scheme 12).The first involves the use of ultrasound in the reaction of (18) (R2= H or Me; R3 = F or CF,) at the nitrile group of (19). Subsequent hydrolysis and cyclization gave fluorinated P-keto- y-butyrolactones.20 The best activating system l5 C. Palazzi L. Colombo and C. Gennari Tetrahedron Lett. 1986 27 1735. 16 1. Paterson M. A. Lister and C. K. McClure Tetrahedron Lett. 1986 27 4787. 17 M.T. Reetz F. Kunisch and P. Heitmann Tetrahedron Lett. 1986 27 4721. 18 T. Mukaiyama N. Yamasaki R. W. Stevens and M. Murakami Chem. Lett. 1986 213. 19 N. Yamasaki M. Murakami and T. Mukaiyama Chem. Lett. 1986 1013. 20 T. Kitazume Synthesis 1986 855. Synthetic Methods Reagents i Zn ultrasound THF; ii H2S04 HzO 25 "C Scheme 12 thus far reported for zinc is a laminated zinc/silver-graphite obtained from CgK/ZnC12/Ag[OCOMe]. This allowed the reaction between ethylbromoacetate and cyclohexanone to proceed in high yield at temperatures as low as -78 "C over twenty minutes.21 Triphenylmethyl perchlorate was used to activate silyl enol ethers (20) towards Michael reaction with enones. The anti :syn ratio in the product was typically 80 :20 at room temperature but could be improved by cooling.22 The first product of this reaction is an enolate anion and this may be used for a further aldol condensation in a tandem reaction (Scheme 13).The product y-acyl-8-hydroxy ketone derivative (21) was produced with good stereoselectivity uia a transition state dominated by steric effects.23 i ii Me,CMe2SiwR3 - R' \ (20) Me 121 1 Reagents i [Ph,C][ClO,]; ii aOH ;iii R4CH0 Scheme 13 An enantiaselective Michael reaction of ethyl acetoacetate with esters of 2- carboalkoxy-a$-unsaturated acids was achieved (Scheme 14) using the chiral enamine (22) synthesized from ethyl acetoacetate and the t-butyl ester of valine. The final product was obtained in up to 93% enantiomer excess.24 Allyl Alkynyl and Alkenyl Anions and their Equivalents.Mixed metal allyl anions RLiMg prepared from allyl magnesium chloride and a lithium amide base may be used for the conversion of esters into enones. A successful reaction is assured since 21 R. Csuk A. Furstner and H. Weidmann J. Chem. SOC.,Chem. Commun. 1986 775. 22 T. Mukaiyama M. Tamura and S. Kobayashi Chem. Lett. 1986 1017. 23 S. Kobayashi and T. Mukaiyama Chem. Lett 1986 221. . 24 K. Tornioka K. Yasuda and K. Koga Tetrahedron Lett. 1986 27 715 and 4611. P. A. Chaloner Me2CH3. R' GCOOR2 COOR2 I,II ~ J& +% COOR' EtOOC COORZ 111 IV (22) Reagents i LDA; ii HCl; iii 20%HCI MeCOOH A; iv CH2N2 J&OOMe Scheme 14 R'AZnBr R' + '& -2; R4 MgBr BrZn R4 R5 \ MgBr Reagents i R'CHO BF,.Et,O (23) Scheme 15 the product is enolized by the strong base and hence unavailable for further rea~tion.~' gem-Dimetallic compounds (23) were also formed on reaction of allyl zinc halides with alkenyl Grignard reagents via a carbometallation process (Scheme 15).Compound (23) underwent condensation with aldehydes or reacted with suc- cessive portions of two electrophiles.26 A facile and stereoselective preparation of allyl stannanes using an ultrasound- accelerated Barbier-type reaction between tributyltin chloride and an allyl chloride has been described; cross-coupling occurred under conditions in which both com- ponents were capable of self-~oupling.~~ Three groups have separately reported the synthesis of a-methylene- y-lactones (25) (Scheme 16) from ethoxycarbonyl allyl stannane (24) and aldehydes.28 The reaction of E-1-phenyl-3-chloro-1-propene with Bu,SnY/ -Ry& COOEt -6 COOEt R (24) (25) Reagents i RCHO BF,.Et20 CH2C12; ii CF,COOH CH2C12 Scheme 16 25 C.Fehr and J. Galindo Helu. Chim. Acta 1986 69 228. 26 P. Knochel and J. F. Normant Tetrahedron Lett. 1986 27 1039 and 1043. 27 Y. Naruta Y. Nishigaichi and K. Maruyama Chern. Lett. 1986 1857. 28 J. E. Baldwin R. M. Adlington and J. B. Sweeney Tetrahedron Lett. 1986 27 5423; K. Uneyama K. Ueda and S. Torii Chem. Lett. 1986 1201; J. Nokami T. Tamaoka H. Ogawa and S. Wakabayashi Chem. Lett. 1986 541. Synthetic Methods 249 aldehydes in the presence of tin(o) (generated in situ from tin(r1) chloride and aluminium powder) gave threo-products (26) with between 90 and 99% ~electivity.~~ Compound (24) also reacted with 1-bromoadamantane in the presence of a radical initiator to give (27) in up to 70% yield.30 Ph Enantiomerically pure 2-2-butenyldiisopinocampheylboranes may be prepared from 2-2- butenyl potassium and P-methoxy diisopinocampheyl borane [derived from (+)-a-pinene] and react with aldehydes to give erythro P-methyl homoallyl alcohols with greater than 99% diastereoselection and more than 95% enantioselec- tivity.The E-isomer (28) gave exclusively a threo product with about 90% enan- tioselectivity (Scheme 17). Since (-)-a-pinene is also readily available this route may be used to yield all four possible stereoisomers of the product with excellent selection.31 Enantioselective (53-84% e.e.) allylation of prochiral aldehydes was achieved using allyl bis(2-methylpropyl)aluminium in the presence of (16) and tin(r1) trif~ate.~~ OH OH 95 5 Reagents i RCHO -78 "C; ii H202 Scheme 17 0R' 0R' Reagent Lewis acid Scheme 18 The reaction of allyl silanes with aliphatic acetals in the presence of a Lewis acid (Scheme 18) was extremely regiospecific and highly syn-selective irrespective of the geometry of (29) or the Lewis acid used.However with aryl aldehyde acetals 2-(29) gave mainly anti-products whilst the E-isomer gave a syn-selective reaction. 29 K. Uneyama H. Nanbu and S. Torii Tetrahedron Lett. 1986 27 2395. 30 J.E. Baldwin R. M. Adlington D. J. Birch J. A. Crawford and J. B. Sweeney J. Chem. Soc. Chem. Commun. 1986 1339. 31 H. C. Brown and K. S. Bhat J. Am. Chem. SOC.,1986 108 5919. 32 T. Mukaiyama N. Minowa T. Oriyama and K. Narasaka Chem. Lett. 1986 97. Z? A. Chaloner The diastereoselection depended on the electronic demand of substituents on the aryl ring and various plausible transition states were proposed.33 A practical and highly stereocontrolled synthesis of 1,3-dienes from allyl silanes is shown in Scheme 19.34 i ii iii vi OH 100O/o Iv R- 75-0 2?o Reagents i BuLi THF; ii [Ti(OCHMe,),] -78 "C; iii RCHO -78 "C; iv Me,COK 25 "C; v H2[S04] THF; vii 30°C 3 h Scheme 19 The hydroboration of alkynes is known to proceed with excellent stereospecificity to yield alkenyl boranes.The hydroboration/ halogenoboration sequence of Scheme 20 allows the preparation of both stereoisomers of the disubstituted alkenyl bromides.35 Analogous reactions were used in the stereospecific synthesis of trisub-stituted alkenes by coupling of alkenyl boranes with alkenyl halides in the presence of palladium(0) catalysts.36 Alkenyl copper compounds produced by alkenylcupration of alkynes have also found further applications (Scheme 21) since they may be readily coupled with alkyl allyl and acyl halides. Their reaction with enones is very much improved by Reagents i R2BHBr.SMe2 Et20 0 "C; ii MeONa MeOH 25 "C; iii Br, CH,Cl, -40 "C; iv MeONa MeOH -40 "C; v BHBr,.SMe, CH,CI,; vi MeOH Scheme 20 33 A.Hosomi M. Ando and H. Sakurai Chem. Lett. 1986 365. 34 Y. Ikeda and H. Yamamoto Bull. Chern. SOC.Jpn. 1986 59 657. 35 H. C. Brown N. G. Bhat and S. Rajagopalan Synthesis 1986 480. 36 M. Satoh N. Miyaura and A. Suzuki Chem. Lett. 1986 1329; N. Miyaura M. Satoh and A. Suzuki Tetrahedron Lett. 1986 27 3745. Synthetic Methods 25 1 . .. ... I II 111 BuLi (BwuLi Bu Reagents i CuBr.SMe2 Et20 -40 "C; ii C2H2 -25 "C 30 min; iii C2H2 0 "C 10 min; iv MeI HMPA Et,O -50 "C -* 0 "C; v Me,SiCI; vi cyclohexenone; vii H20 Scheme 21 the presence of trimethylchlorosilane and this was also found to be the case with other organocopper compounds and other unsaturated carbonyl compounds.37338 The efficiency of the conversion of alkenyl iodides into alkenyl chromium com- pounds using chromium(I1) chloride was initially found by Kishi to be strongly dependent on the source of the chromium(I1) salt.However addition of O.l-lo/~ nickel(11) chloride removed this dependence and allowed coupling with aldehydes to occur under very mild conditions with a high tolerance for other functional groups.39 Numerous papers this year have reported the coupling of 1-alkynes with alkenyl and more particularly aryl and heteroaryl halides in the presence of base copper salts and a palladium(0) catalyst. Among the more interesting examples was the reaction of (30) the product being cyclized to give an indole derivative (Scheme 22).40 Alkynylzinc compounds reacted again under palladium(0) catalysis only with E-alkenyl halides giving (31) in excellent stereoisomeric purity (Scheme 23).4' R Reagents i RCECH [Pd(PPh3)2C1,] Et,N 100 "C; ii EtONa EtOH Scheme 22 R R Br RCH=CHBr+ClZnC_C-SiMe -** +w %Me3 E+Z (31) Reagent [Pd( PPh,),] Scheme 23 37 H.Furber R. J. K. Taylor and S. C. Burford J. Chem. SOC.,Perkin Trans. I 1986 1809. 38 A. Alexakis J. Berlan and Y. Besace Tetrahedron Lett. 1986 27 1047. 39 H.Jin J. Uenishi W. J. Christ and Y. Kishi. J. Am. Chem. Soc.. 1986 108 5644. 40 T. Sakamoto Y. Kondo and H. Yamanaka Heterocycles 1986 24 31 and 1845. B. P. Andreini A. Carpita and R. Rossi Tetrahedron Lett. 1986 27 5533. P. A. Chaloner The 'new' metal for this year was vanadium and alkynylvanadium compounds underwent oxidative nucleophilic addition to aldehydes to give qp-alkynyl ketones (32) (Scheme 24).42Allenyl boronic and chiral allenyl boronates& have been used in very highly diastereoselective and enantioselective additions to carbonyl groups (Scheme 25).1 I1 R-CrC-Li -R-C=C-VCl -R-CZC-COR' (32) Reagents i VCI, CH2CI, -78 "C; ii R'CHO CH2C12 -78 "C Scheme 24 OH H R02C OH Reagents i CH,=C=CHB(OH),; ii H,O,; iii PhMe; iv OCH0 ROzCXOH H Scheme 25 Miscellaneous. There have been further reports of new reagents for carbonyl alkenyla- tion. [ClW(O)=CH,] converted 1-phenylethanone into 2-phenylpropene4' and the tungsten Wittig reagents [R'R'C= W(OCH2CMe3)4] reacted with esters and lac- tones at room temperature and amides at 50°C.These species should prove more versatile than the Tebbe reagent since numerous substitution patterns can be obtained and by varying the other ligands at tungsten reagents of different chemoselectivities were The cyclic pentavalent phosphorus compound (33) may be opened to (34) and thus represents an extremely stable reagent for ketone methyleneation needing 42 T. Hirao D. Misu and T. Agawa Tetrahedron Lett. 1986 27 933. 43 N. Ikeda K. Omori and H. Yamamoto Tetrahedron Lett. 1986 27 1175. 44 N. Ikeda I. Arai and H. Yamamoto J. Am. Chem. Soc. 1986 108 483. 4s T. Kauffmann R. Abeln S. Welke and D. Wingbermiihle Angew. Chem. Int. Ed. Engl. 1986 25 909 and 910. 46 A. Aguero J. Kress and J. A. Osborn J. Chem. SOC.,Chem. Commun. 1986 531. Synthetic Methods 253 neither base nor solvent for successful reaction?' A Wittig-like synthesis of 1,l-diiodoalkenes was achieved using Ph,P=CI, formed at 0 "C from triphenylphos- phine and carbon tetraiodide.It reacts readily with aldehydes but not with ketones in the presence of zinc The scope of Peterson reactions has been extended (Scheme 26).49,50 2 -BuCHYCHMe PhS SiMe Li %Me3 Reagents i LiNp TNF -78 "C; ii MeCHO THF -78 "C-* 0 "C Scheme 26 MeO? 8'20Me MeO? #''OMe COH (35) Reagent MeMgI Scheme 27 Many workers continue to report examples of the addition of organometallic reagents to carbonyl compounds. Amongst the most interesting examples are those in which enantioselective reaction is achieved using an appropriate chiral auxiliary.The reaction of Grignard reagents with the chiral a-ketoacetal (35) gave up to 98% optical yield (Scheme 27). The presence of the methoxy groups was critical to successful reaction suggesting that these may be involved in chelation of the incoming n~cleophile.~~ The chirally modified methyltitanium reagent (36) reacted with aldehydes in between 31 and 90% enavtiomer excess,52 whilst (37) proved a useful 47 H. Daniel and M. Le Corre Tetrahedron Lett. 1986 27 1909. 48 F. Gavifia S. V. Luis P. Ferrer A. M. Costero and J. A. Marco J. Chem. Rex (S) 1986 330. 49 D. J. Ager J. Chem. SOC.,Perkin Trans. I 1986 183 and 195. 50 S. Hackett and T. Livinghouse J. Org. Chem. 1986 51 879. Y. Tamura H. Kondo H. Annoura R. Takeuchi and H. Fujioka Tetrahedron Lett.1986,27,81and 21 17. 52 M. T. Reetz T. Kukenhohner and P. Weinig Tetrahedron Lett. 1986 27 5711. P. A. Chaloner catalyst for the enantioselective reaction of aldehydes with dialkyl zinc corn pound^.^^ Addition of a methyltitanium reagent of reduced Lewis acidity to (38) was not chelation-controlled giving (39) with more than 99% selectivity (Scheme 28).54 Homoenolate anions may be generated readily from the mixed acetal (40) and could be coupled with aryl halides under palladium(0) catalysis. A homo-Refor-matsky reaction occurred in the presence of titanium tetra~hloride.~~ Cerium homoenolates prepared from P-bromoesters by contrast gave lactones (41) (Scheme 29).56 Me3CMezSi0\ //0 M e3 CMe SiOMOH ..m -Me--Me Me H Et H Et (38) (39) Reagent [MeTi(OCHMe,)J Scheme 28 fyoR C1,Ti.Ph LOOR R1 RZ -COOMe BrCe Reagents i ZnCI,; ii PhI; iii [Pd{P(C,H4-4-Me),},C12]; iv TiCI4; v PhCHO Scheme 29 The continuing search for more selective reagents has again led to the employment of some of the more 'exotic' metals. Two groups have reported the iodomethylation of carbonyl compounds [e.g. (42)] which occurs both in the presence of samarium metal and samarium iodide (Scheme 30). a-Halogenoketones yielded cyclopro- 53 M. Kitamura S. Suga K. Kawai and R. Noyori J. Am. Chem. SOC.,1986 108 6071. 54 M. T. Reetz and M. Hullmann J. Chem. SOC.,Chem. Commun. 1986 1600. 55 E. Nakamura and I. Kuwajima Tetrahedron Lett. 1986 27 83; E. Nakamura H. Oshino and I.Kuwajima J. Am. Chem. Soc. 1986 108 3745. 56 S. Fukuzawa T. Fujinami and S. Sakai J. Chem. Soc. Chem. Cornmun. 1986 475. Synthetic Methods (42) Reagents CH,I, Sm THF 0°C Scheme 30 pan01s.~' Organ~tin,~~ vanadium,59 and manganese6' reagents have all been shown to react selectively with acyl halides to give ketones. [RMnX] will also react with aldehydes in the presence of ketones with greater than 99% selectivity for the aldehyde. Tris(trimethylsily1amido)methyl uranium has been recommended as a highly selective nucleophilic methylating agent.61 Organozincates R,ZnMgBr or R,ZnLi have proved excellent reagents for regioselective Michael attack on enones; only one group is generally transferred.62 Enantioselective addition of a chiral cuprate to cyclohexenone could be achieved in up to 92% enantiomer excess (Scheme 31); the structure (43) was proposed for the transition state.63 Asymmetric 1,4-addition to N-enoyl sultams (44) occurred with excellent diastereoselectivity; the products were converted into chiral P-hydroxy Ph&.p.-NMe, Reagents i MeI THF -78 "C; ii N THF -78 "C; ;I OH Me iii CuI THF Me,S -35 "C; iv BuLi MeI -78 "C; v cyclohexenone -78 "C Scheme 31 X = I or THF; S = THF; (43) R = Et Bu or Me3COCH 57 T. Imamoto T. Takeyama and H. Koto Tetrahedron Lett. 1986,27,3243; T. Tabuchi J. Inanaga and M. Yamaguchi Tetrahedron Lett. 1986 27 3891. 58 J.-B. Verlhac and J.-P. Quintard Tetrahedron Lett. 1986 27 2361. 59 T. Hirao D. Misu K. Yao and T. Agawa Tetrahedron Lett.1986 27 929. 60 G. Cahiez J. Rivas-Enterrios and H. Granger-Veyron Tetrahedron Lett. 1986 27 4441 and 4445. 61 A. Dormond A. Aaliti and C. Moise Tetrahedron Lett. 1986 27 1497. 62 R. A. Kjonaas and E. J. Vawter J. Org. Chem. 1986 51 3993; W. Tuckmantel K. Oshima and H. Nozaki Chem. Ber. 1986,119 1581; R. A. Watson and R. A. Kjonaas Tetrahedron Lett. 1986,27 1437. 63 E. J. Corey R. Naef and F. J. Hannon J. Am. Chem. SOC.,1986 108 7114. 256 P. A. Chaloner esters (Scheme 32). 1,4-Hydride addition using L-Selectride was also very stereoselec- The asymmetric synthesis of a-substituted carbonyl compounds has been achieved by attack of an organoaluminium compound on an a$-unsaturated chiral acetal. The regioisomeric products could be readily separated and cleaved (Scheme 33).65 V I--+ so2 SiMe2Ph (44) 1 ii iii OH SiMe2Ph 92->98% e.e.Reagents i RLi Cur PBu, EtAICI,; ii LiOH H20 THF; iii CH2N2; iv H[BF4]; v 3-CI-C,H4C03H Scheme 32 CONMe2 Rlq$-CONMe2 R2 li H 5' 4-RI+O R3 YONMe2 *CONMe2 R2 I ii iii ~2 = H 5' F3 A R'Y R' COOH R2 Reagents i RiAl 5-25 "C; ii 03,MeOH; iii [Mn04]-Scheme 33 64 W. Oppolzer R. J. Mills W. Pachinger and T. Stevenson Helu. Chirn.Acta 1986,69 1542; W. Oppolzer and G. Poli Tetrahedron Lett. 1986 27 4717. 65 K. Maruoka S. Nakai M. Sakurai and H. Yamamoto Synthesis 1986 130. Synthetic Methods Further work on the reductive coupling of ketones to give pinacols has appeared.For example magnesium in graphite is effective for reaction of both aldehydes and ketones and gives excellent yields even in the case of benzophenone which is a poor substrate under McMurray conditions.66 The similarly hindered compound (46) was prepared uia the tin derivative (45) (Scheme 34).67 II 4 / Q$g '0 Reagents i [(Me,(PhS)Sn},] hv; ii NaOH H20 Scheme 34 Transition metal-catalysed reactions have continued to dominate the fields of carbonylation and carboxylation. Of particular interest have been the new double carbonylations reported for aryl and benzyl halides in the presence of [co,(co)8] yielding a-keto acids.68 Compound (47) prepared from 1-butene Et2NH and [ Pd( MeCN),C12] in a carbon monoxide atmosphere reacted with piperidine to give (48).Chromatography on silica promoted amine elimination giving (49) in a surpris- ingly high 75% yield.69 Aryl benzyl alkenyl and ally1 iodides and triflates were homologated to aldehydes using Bu3SnH-CO with palladium(0) as a ~atalyst,~' the Et2N' COCON ) 'COCON ) reaction being tolerant of a wide range of functional groups. Electroreductive carboxylation of aryl and benzyl halides using palladium(0) or nickel(o) catalysts gave a clean and convenient synthesis of carboxylic acids.71 Electrochemical reduc- tion of 3-halogeno-/3-lactams in an atmosphere of C02 yielded 3-carboxy-/3-lactams which are otherwise rather difficult to prepare.72 66 R. Csuk A. Fiirstner and H. Weidmann J. Chem. SOC.,Chem. Commun. 1986 1802. 67 H. Fobbe and W.P. Neumann J. Organomet. Chem. 1986 303 87. 68 F. Francalanci E. Bencini A. Gardano M. Vicenti and M. FOB J. Organomet. Chem. 1986,301 C27. 69 F. Ozawa M. Nakano I. Aoyama T. Yamamoto and A. Yamamoto J. Chem. SOC.,Chem. Commun. 1986 382. 70 V. P. Baillargeon and J. K. Stille J. Am. Chem. SOC.,1986 108 452. 71 S. Torii H. Tanaka T. Hamatani K. Morisaka A. Jutand F. Huger and J.-F. Fauvarque Chem. Lett. 1986 169; J. F. Fauvarque A. Jutand and M. Francois Noun J. Chim. 1986 10 119. 72 M. A. Casadei F. M. Moracci and A. Inesi J. Chem. SOC.,Perkin Trans. 2 1986 419. P. A. Chaloner Homoallyl alcohols such as (50) were efficiently prepared by reductive coupling of allylic acetates with carbonyl compounds using palladium(o)/samarium( 11) iodide (Scheme 35).The reaction is thought to involve samarium iodide-induced elec- trophilic substitution of an allyl palladium complex.73 Ring-opening of P-epoxysulphones sulphoxides and esters (51) with Grignard reagents has been achieved at -60 "C without loss of chirality using a copper catalyst (Scheme 36). Such epoxides are generally extremely labile and undergo facile base-promoted eliminative fission to allyl Reagents SmI, [Pd( PPh,),] THF 0 "C (SO) Scheme 35 O h R +R'MgBr -+ KTR OH R = SO,Ph SOPh or COOEt R' = Ph or alkyl Reagents CuI Et20 THF -60 "C 1 min Scheme 36 -SiMe2Ph I + (PhMe2Si)3MnMgMe -Me(CHJ9 Me(CHh (52) Reagents THF 0 "C Scheme 37 Alkenyl and allyl silanes such as (52) were synthesized by cross-coupling of alkenyl and allylic compounds with trisilylmanaganese methyl magnesium (Scheme 37).The reagent is prepared from PhMezSiMgMe and Liz[MnCl4]. The reaction is stereospecific for E-substrates but usually only stereoselective for the 2-analogues. Stereospecific synthesis of 2-products was accomplished at -95 0C.75p-Ketosilanes and p-ketophosphonates were synthesized from a-halogenoketones uia a novel Umpolung approach (Scheme 38). This route is complementary to the Arbusov process and also allows the synthesis of fluoroalkyl phosphonate derivatives which are insufficiently nucleophilic for the Arbusov reaction.76 73 T. Tabuchi J. Inanaga and M. Yamaguchi Tetrahedron Lett. 1986 27 1195. 74 R. Tanikaga K. Hosoya and A. Kaji J. Chem. Soc. Chem.Commun. 1986 836. 75 K. Fugami K. Oshima K. Utimoto and H. Nozaki Tetrahedron Lett. 1986 27 2161 76 P. Sampson G. B. Hammond and D. F. Weimer J. Org. Chem. 1986 51 4342. Synthetic Methods 0 0 0 iv,v,vi LB~ t-Ph ), Ph SiMe3 Reagents i Li[N(SiMe3)2] THF -65 "C; ii [Me,C]Li -65 "C; iii (EtO),P(=O)CI -100 "C; iv Li[N(SiMe,)2] THF -78 "C; v Me,SiCI -78 "C; vi BuLi -78 "C Scheme 38 Aryl derivatives of dimethyl malonate (53) are not readily available from car- banionic routes but may be obtained by a ceric ammonium nitrate-catalysed radical reaction (Scheme 39). The site-selectivity observed in the reactions with toluene and methoxy benzene suggest that the intermediate the [ *CH(COOMe)2] radical is ele~trophilic.~~ In another radical reaction (Scheme 40) ketones were coupled with electron-deficient alkenes in the presence of samarium iodide.78 C6H6 + CH,(COOMe) + PhCH(COOMe) (53) Reagents [ NH,],[Ce( NO,),] MeOH 25 "C Scheme 39 R2 Reagents i CH2=CHCOOEt; ii ROH Scheme 40 Cyc1ization.-Free-radical cyclizations continue to attract considerable attention.The well-established formation of radicals by halide abstraction was used to initiate the cyclization of silyl enol ethers such as (54) to give (55) (Scheme 41) as a 1 1 mixture of diastereoi~omers.~~ A photochemical process (Scheme 42) was used to initiate reaction of (56) to give a carbapenam.80 The phenylseleno group may also be abstracted by triphenyltin radicals; Scheme 43 shows a new synthesis of cyclopen-tanes using an ester enolate rearrangement in conjunction with radical cyclization.81 Intramolecular aromatic cyclization of alkenyliodonium salts (57) occurs readily on heating (Scheme 44); intermolecular arylation may also be accomplished.** The 77 E.Baciocchi D. Dell'Aira and R. Ruzziconi Tetrahedron Lett. 1986 27 2763. ?a S. Fukuzawa A. Nakanishi T. Fujinami and S. Sakai J. Chem. SOC.,Chem. Commun. 1986 624. 79 H. Urabe and I. Kuwajima Tetrahedron Lett. 1986 27 1355. J. Knight P. J. Parsons and R. Southgate J. Chem. SOC.,Chem. Commun. 1986 78. A. Y. Mohammed and D. L. J. Clive J. Chem. SOC.,Chem. Commun. 1986 588. 82 M. Ochiai Y. Takaoka K. Surni and Y. Nagao J. Chem. SOC.,Chem. Commun. 1986 1382. €? A. Chaloner Reagents i Bu3SnH AIBN C6HS;ii HCl MeOH Scheme 4.1 0dx-oa (56) Reagents C6H6 hv Scheme 42 02C( CH2)$e P h 11 111 .....iz(sep' C02SiMe2CMe3 602Me C02Me Reagents i CICO(CH,),SePh py Et,O ii. LDA. THF. -78 "C; iii (Me3)CMe2SiCI HMPA. THF; iv [Bu,N]F; v CH2N2;vi Ph3SnH AIBN Scheme 43 SiMe3 'IPh BFL Reagents i PhIO BF,.Et,O CHIC], 0 "C; ii CD30D 60 "C Scheme 44 Synthetic Methods 26 1 Pummerer type reaction of a-acyl sulphides with [ PhI(OCOCF,),] generates the cation (58) which is readily cyclized (Scheme 45).83A cationic cyclization of (59) to (60) initiated by SnCl, presumably involves the same type of intermediate. The reaction is extremely stereospe~ific.~~ Enantioselective cyclization of unsaturated aldehydes such as (61) was catalysed with up to 90% e.e.using a chiral Lewis acid (Scheme 46) but the success of the reaction is strongly dependent on substrate structure.85 rOCOCF3 PhI 13 + H -. SMe -QINX -aNxre QL E LoSMe I I I Ph Ph J Reagents [ PhI(OCOCF,),] CICH,CH,CI 25 "C Ph Scheme 45 Reagent Scheme 46 83 Y. Tamura Y. Yakura Y. Shirouchi and J. Haruta Chem. Pharm. Bull. 1986 34 1061. 84 L. E. Overman A. Casteiiada and T. A. Blumenkopf J. Am. Chem. Sac. 1986 108 1303 85 S. Sakane K. Marouka and H.Yamamoto Tetrahedron 1986.42 2203. P. A. Chaloner Pyrrolidine synthesis has been accomplished by palladium-catalysed cyclization of enynes such as (62) (Scheme 47). Compounds (63) and (64) do not interconvert by isomerization and the proportions of each product depended on the substituent R and the ligand L.The best selectivity for (64) is obtained with a diimine ligand such as (65).86Related pyrrolidines (66),were obtained by reaction of a trimethylene methane nickel complex with imines (Scheme 48); in this instance the palladium analogue gave much poorer result^.^' (62) (63) (64) Reagents Pd(OCOMe), L Scheme 47 Reagent [Ni{P(OEt),},] (66) Scheme 48 I CY Ph Ph Reagents i 0 "C;ii 25 "C; iii 100 "C; iv PhNC Scheme 49 B. M. Trost and S.-F. Chen J. Am. Chem. Soc. 1986 108 6053. 87 M. D. Jones and R. D. W. Kemmitt J. Chem. Soc. Chem. Commun. 1986 1201. Synthetic Methods 263 A new route to pyrroles shown in Scheme 49 involves a template synthesis with alkenyl carbene complexes and isonitriles.With aryl isonitriles as the substrates a further cyclization yielded S-carbolines.88 Cycloadditions and Annu1ations.-Reactions Forming Six-membered Rings. A com-mercial microwave oven has been used to reduce the time required for Diels-Alder Claisen and ene reactions.89 Enantioselective Diels- Alder reactions such as the conversion of (67) into (68) were promoted by chiral Lewis acids including (69) and (70).90*91 i ii ql q) iii iv a 7 O\ B,o Ph 0'' '0 HO 0 HO 0 QM~ (67) (68) 70-9 0'/' 98% e.e. \/ \/ MPh Reagents i BH3 THF MeCOOH 20 "C; ii (69); iii ;iv H20 Scheme 50 Ph HO HO Ph Ph ,Ph P h"P h (69) [MoO,(acac),] was used to catalyse the [4 + 21 cycloaddition of (71) to the aldehyde (72) in up to 58% yield (Scheme 51).The reaction was largely but not entirely stereoselective and the product was converted into the Prelog-Djerassi acto one.^^ A new and facile synthesis of 1,2-dimethylenecyclohexaneand [6,6] and [6,7] fused-ring systems was achieved by a double elimination from (74) (Scheme 52). Compound (73) may thus be regarded as a 2,2'-biallyl radical ~ynthon.~~ 88 R. Aumann and H. Heinen Chem. Ber. 1986,119,3801; R. Aumann H. Heinen C. Kriiger and Y.-H. Tsay Chem. Ber. 1986 119 3141. 89 R. J. Giguere T. L. Bray S. M. Duncan and G. Majetich Tetrahedron Let?. 1986 27 4945. 90 T. R. Kelly A. Whiting and N. S. Chandrakumar J. Am. Chem. SOC.,1986 108 3510. 91 K. Narasaka M.Inoue and N. Okada Chem. Lett. 1986 1109. 92 Y. Yamamoto H. Suzuki and Y. Moro-Oka Chem. Lett. 1986 73. 93 A. Hosomi K. Otaka and H. Sakurai Tetrahedron Lett. 1986 27 2881. P. A. Chaloner BzOk+l.-Bzon (71) (72) Reagent [MoO,(acac),] Scheme 51 MeOOC SiMe gCOOMe + SiMe3 xNMe2 + MeOOC MeOOC. X N M e (73) (74)I i ii iii MeOOC MeOOC. Reagents i MeI MeCN; ii CsF MeCN; iii CH2=CHCOOMe Scheme 52 There has continued to be considerable interest in cycloaddition reactions medi- ated by cobalt complexes including pyridine syntheses from dienes and nit rile^^^ and alkynes and nit rile^.'^ The cobalt-catalysed one-step assembly of aromatic steroids (Scheme 53) could be halted at the intermediate (75).96 Et YMe OMe i ii -HO Reagents i [C~CO(CO)~] hv xylene 1 h; ii decane A 20 h Scheme 53 94 B.Potthoff and E. Breitmaier Synthesis 1986 584. 95 G.Vitulli S. Bertozzi R. Lazzaroni and P. Salvadori J. Organomet. Chem. 1986 307 C35. 96 S. H. Lecker N. H. Nguyen and K. P. C. Vollhardt J. Am. Chem. Soc. 1986 108 856. Synthetic Methods 265 The annulation of methanoylcyclohexanones with enamines gave mixtures of the alcohol (76) and the ene-dione (77). Conversion of (76) into (77) was accomplished in CF,COOH giving (77) in 84% yield overall (Scheme 54). This reaction is distinctive in that the new ring is attached to the a and P-carbon atoms rather than the a-carbon and the carbonyl. It represents an example of a small but growing number of reactions in which a six-membered ring is created from two three-carbon fragment^.^' 111 Scheme 54 Reactions Forming Fiue-membered Rings.The 1,3-dipolar cycloaddition of the pyridinium ylide (78) to dimethyl acetylene dicarboxylate yielded (79) after hydrogen transfer to the dipolarophile (Scheme 55). The yield was enhanced and the reaction time greatly reduced by conducting the reaction under ultrasonic irradiati~n.~~ Pyrrolidines were prepared from phenylthioamines as shown in Scheme 56; the COOMe0,-COPh -\@COOMe COPh - COOMe WCOOMe COPh (78) (791 Reagent i Me00C-CEC-COOMe Scheme 55 'uCooMe Me,SiCH2-N-CH2SPh -i ii iii I CHzPh i Ph Reagents i AgF MeCN; ii R-C_C-COOMe; iii DDQ Scheme 56 97 W. L. Meyer M. J. Brannon A.Memtt and D. Seebach Tetrahedron Lett. 1986 27 1449. 98 M. T. GandPsegui and J. Alvarez-Builla J. Chem. Res. (S) 1986 74. 266 P. A. Chaloner intermediate is the dipolarophile (80).99Trimethylenemethane palladium(o) formed in situ underwent cycloaddition to (81) (Scheme 57) in the synthesis of 3-methylene cyclopentenes.loo Cyclopentannulation has been accomplished using methyl 3-phenylsulphonyl orthopropanoate (Scheme 58). The final cyclization of the silyl enol ether was accomplished using Me,SiOTf as the Lewis acid.'" A new synthesis of cyclopen-tenones and cyclohexenones from amides has been noted (Scheme 59). The cycliz- ation of an alkenyl lithium compound onto a carboxamide is unprecedented.lo2 (81 1 R3 R' R',R' are electron-withdrawing groups Reagents i MeCOO SiMe3 ;ii Pd(OCOMe)2 P(OCHMe,),; iii flash vacuum pyrolysis R3 Scheme 57 OSiMe3 I ... ... + m 1 11 111 PhSO ___ IV -C(OMe)3 I SOzPh Reagents i BuLi THF HMPA -78 "C; ii cyclohexenone -78 "C; iii Me3SiC1 Et,N -78 "C -* $25 "C; iv Me3SiOTf CH2CI2 -78 "C Scheme 58 Me& Me3Si 1 ii iii -Ia -M~+ I Et2N Ph Ph Reagents i LDA PhCH2CONEt2 THF; ii [Me,C]Li; iii [NH,]CI H20 Et20 Scheme 59 99 A. Padwa W. Dent H. Nimmesgern M. K. Venkatramanan and G. S. K. Wong Chem. Ber. 1986 119 813. 100 B. M. Trost J. M. Balkovec and S. R. Angle Tetrahedron Lett. 1986 27 1445. 101 S. De Lombaert I. Nemery B. Roekens J. C. Carretero T. Kimmel and L. Ghosez Tetrahedron Lett. 1986,21 5099.102 H. Sawada M. Webb A. T. Stoll and E. Negishi Tetrahedron Lett. 1986 27 775. Synthetic Methods Other Ring Sizes. Copper complex containing zeolites were successful catalysts for alkene cyclopropanation by ethyl diazoacetate (Scheme 60). The activity of the catalyst depended on the sodium exchange level and this promoter gave lower amounts of polymer than the more conventional cataly~ts.''~ Two stereoselective syntheses of p-lactam derivatives have been reported (Scheme 61). In the first the product obtained is largely cis suggesting that the reaction does not involve a ketene cycloaddition.'04~'05 78 22 Reagents N2CHCOOEt zeolite NaCuX-57 A Scheme 60 0 Reagents i Et3N CH2C12 5-10 "C; ii py 25 "C Scheme 61 Rearrangements and Fragmentations.-The Claisen rearrangement of (82) gave a synthesis of the unusual 5,6-unsaturated 8-membered lactones (Scheme 62).Although a reasonable chair transition-state could be envisaged for the trans-isomer w" I _.* *Yo 0 Ox0SePh (82) II 0 Reagents DBU xyfene Mg[SO,] A Scheme 62 103 J. C. Oudejans J. Kaminska A. C. Kock-van Dalen and H. van Bekkum Red. Trav. Chim. Pays-Bas 1986 105 421. 104 S. D. Sharma S. Kaur and U. Mehra Indian J. Chern. Sect. B 1986 25 141. lo' D. K. Dutta R. C. Boruah and J. S. Sandhu Heterocycles 1986 24,655. P. A. Chaloner the cis-analogue was thought to react via a boat transition-state.lo6 A Claisen rearrangement was also the key step in the regiospecific synthesis of P,y-unsaturated ketones from ally1 alcohols (Scheme 63).'07 The [2,3] Wittig rearrangement followed by a Peterson alkenylation sequence has provided an extremely stereoselective synthesis of dienynes (Scheme 64).Both products were produced from the same precursor and were formed with more than 95% selectivity."* CHO i or ii iii iv R2 R R' R' R' R5 R3 / R2 0 Reagents i RCOCHN, BH3 Et,O; ii NaH; iii R q ;iv PCC; v Me,SiCI Et,N DMF; vi Na[IO,] Scheme 63 -SiMe3 SiMe3 97% E 95% E 96% threo SiMe3 I J' Reagents i BuLi THF -85 "C; ii BF,.Et,O CH,CI,; iii KH THF Scheme 64 Tsuchihashi's group have reported further preparations of chiral synthons bearing alkynyl groups via organoaluminium promoted pinacol type rearrangements (Scheme 65).'09 The Lewis acid promoted rearrangement of a,P-epoxy oximes was found to lead to the synthesis of diketospiroalkanes.The diketospiranes produced by this route 106 R. W. Carling and A. B. Holmes J. Chem. SOC.,Chem. Commun. 1986 325. 107 J. L. C. Kachinsky and R. G. Salomon J. Org. Chem. 1986 51 1393. 108 K. Mikami T. Maeda and T. Nakai Tetrahedron Lett. 1986 27 4189. 109 K. Suzuki T. Ohkuma M. Miyazawa and G. Tsuchihashi Tetrahedron Lett. 1986 27 373. Synthetic Methods Me& OH >99% threo Reagents i Me,AI CHCI, C,H,; ii Li[AlH,] -100°C Scheme 65 were isomeric with those from the rearrangement of the corresponding a$-epoxyketones (Scheme 66)."' Opening of the cyclopropyl derivative (83) with [Hg(OR),] is extremely regio- and stereoselective (Scheme 67).After reduction with Li[AlH4] the overall transfor- mation achieved was that of an allyl alcohol into a 2-methyl-1,3-diol; this process complemented the hydroboration of a secondary allyl alcohol."' II 111 IV -Reagents i BF3.Et20;ii Na[BH,]; iii TiCI,; iv PCC Scheme 66 Reagents i [Hg(OR),]; ii NaCI; iii Li[AIH,] Scheme 67 'lo R. D. Bach M. W. Tubergen and R. C. Mix Tetrahedron Lett. 1986 27 3565. "' D. B. Collum W. C. Still and F. Mohamadi J. Am. Chem. SOC.,1986 108 2094. 270 l? A. Chaloner 3 Functional Group Modifications Oxidation.-Additions to C=C. There have been numerous reports of new methodology for the conversion of alkenes into epoxides. Two groups separately have reported the use of hydrogen peroxide with a tungstic acid or pertungstate catalyst in a buffered medium.Allylic alcohols were particularly reactive.Il2 Epoxida- tion of such substrates by Me,COOH in the presence of [Bu2SnO] was generally found to be somewhat more selective than reactions using [VO(a~ac),].''~ Elec- trophilic alkenes underwent stereo- and regiospecific epoxidation using RLi-Me,COOH with the esters of chiral alcohols reacting with up to 65% diastereofacial selectivity.' l4 The enantioselective epoxidation of allyl alcohols by the Sharpless reaction has again been much in evidence this year and has been re~iewed."~ A particularly elegant demonstration of the power of this process is shown in Scheme 68 in which both enantioselective epoxidation and kinetic resolution are employed to synthesize the four stereoisomers of secondary allyl alcohols all with excellent selectivity."6 The well-known conversion of alkenes into cis-diols by osmium(v1rI) oxide may be achieved in an enantioselective manner in the presence of chiral amines such as (84) and (85) (Scheme 69)."' Novel reagents containing iodine(rI1) such as (86) convert alkenes via an electrophilic process into dioxygenated derivatives.' '*In the presence of PhIO sodium azide was added to alkenes to give vicinal diazides as the major product^."^ Oxymercuration of (87) yields (88) but demercuration of these intermediates could be induced to follow a different course from those of simple alkenes.The amount of threo product was increased in non-polar solvents giving excellent selectivity.By comparison conventional demercuration with Na[ BHJ-EtOH was extremely sensitive to the amount of hydride present and stereoselection was usually modest.'20 Other Oxidations. Chemoselective oxidation of primary alcohol groups in diols was achieved by zirconocene-catalysed hydrogen transfer to cyc1ohexanone.l2' Selective oxidation of secondary alcohols in the presence of primary ones could by contrast be accomplished using [NH4I2[Ce( NO,),]-Na[ Br03],122 Me,COOH in the presence or of a range of molybdenum c~mplexes,'~~ K2[FeO,] and a phase-transfer 112 D. Prat and R. Lett Tetrahedron Lett. 1986,27,707;J. Prandi H. B. Kagan and H. Mimoun Tetrahedron Lett. 1986 27 2617. 113 S. Kanemoto T.Nonaka K. Oshima K. Utimoto and H. Nozaki Tetrahedron Lett. 1986 27 3387. 114 C. Clark P. Hermans 0. Meth-Cohn C. Moore H. C. Taljaard and G. van Vuuren J. Chem. SOC. Chem. Commun. 1986 1378. 115 A. Pfenninger Synthesis 1986 89. 116 Y. Kitano T. Matsumoto and F. Saio J. Chem. SOC. Chem. Commun. 1986 1323; Y. Kitano T. Matsumoto Y. Takeda and F. Sato J. Chem. SOC.,Chem. Commun. 1986 1732. 117 M. Tokles and J. K. Snyder Tetrahedron Lett. 1986 27 3951; T. Yamada and K. Narasaka Chem. Lett. 1986 131. 118 N. S. Zefirov V. V. Zhdankin Yu. V. Dan'kov V. D. Sorokin V. N. Semerikov A. S. Koz'min R. Caple and B. A. Berglund Tetrahedron Lett. 1986 27 3971. 119 R. M. Moriarty and J. S. Khosrowshahi Tetrahedron Lett. 1986 27 2809. 120 F.H. Gouzoules and R. A. Whitney J. Org. Chem. 1986 51 2024. 12' T. Nakano T. Terada Y. Ishii and M. Ogawa Synthesis 1986 774. 122 S. Kanemoto H. Tomioka K. Oshima and H. Nozaki Bull. Chem. SOC.,Jpn. 1986 59 105. 123 K. Yamawaki T. Yoshida T. Suda Y. Ishii and M. Ogawa Synthesis 1986 59; Synth. Commun. 1986 16 537. Synthetic Methods 271 .. ... II 111 I Me3si+R1 OH + Me3si-YR1 ~ Me3SiyR1 iv Me3Si R OH OH ,/ *" ii iii / EE = ethoxyethyl Reagents i Me,COOH [Ti(OCHMe,),] L-(+)-DIF'T; ii CH,=CHOEt H+; iii R2MgBr CuI; iv Me,COOH [VO(acac),]; v KH THF then HCI; vi H2[S04] MeOH Scheme 68 catalyst.'24 Silver ferrate was a better oxidant and needed no phase-transfer agent whilst barium ferrate was advocated as a safe versatile and non-pollutant oxidant for a wide range of alcohols.'25 Oxidative deprotection of alcohols occurred with (89); this is a particularly mild reagent leaving even a sensitive p-lactam functionality intact (Scheme 70).'26 Further stereoselective a-oxidations of enolates have been reported this year.Dibenzyl peroxycarbonate was used in the oxidation of (90) to the carbonate of the hydroxycarbonyl compound in >99 :1diastereomer ratio (Scheme 71) and a-amino 124 K. S. Kim Y. H. Song N. H. Lee and C. S. Hahn Tetrahedron Lett. 1986 27 2875. 125 H. Firouzabadi D. Mohajer and M. E. Moghaddam Synth. Commun. 1986 16 211 and 723. I26 F. P. Cossio J. M. Aizpurua and C. Palomo Can. J. Chem. 1986 64 225. I? A. Chaloner Q I aNpxy H '1 Ph-I ,OH a::: OMS (84) (85) (86) Hg0C0Me 1i &COOMe i_ COOMe -&cooMe Me0 H Me0 H (87) (88) threo erythro = 95 5 Reagents i [Hg(OCOMe),] MeOH ii HS(CH,),SH Et,N MeOH Scheme 69 R' R2 R' R2 0 II CI-Cr-OSiMe3 II 0 (89) R' = PhO R2 = Ar R3 = H Me$i or (Me3C)Me2Si Reagent (89) Scheme 70 Reagents i Li[ N(NMe,),]; ii (PhCH20COOS2 Scheme 71 Synthetic Methods and a-hydrazino derivatives were prepared ~imi1arly.l~' An alternative approach is the oxidation of an achiral enolate by a chiral camphonyl sulphonyl oxaziridine (Scheme 72).Ketone ester and amide enolates were all successfully oxidized in some cases giving excellent optical yields particularly from Z-enolates.'28 i ii Ph-COOMe -Ph Scheme 72 In the area of sulphide oxidations new protocols have been developed for simple reactions and further progress has been made in the area of enantioselective oxidations.Selectivity for sulphoxides was excellent using 0,-[NH,][Ce( NO,),] (which involves a radical process).129 Chiral systems have ranged from the well- known [Ti(OCHMe2),]-(+)-DET130 to Na[IO,]-bovine serum albumin'31 and Na[ IO,]-[A-Ni( l,10-phen),]-montmorillonite.'32 Tartaric acid derivatives could also be used as chiral auxiliaries for PhIO generating (91) in sit^',^ as an oxidant. In all these instances selectivity for the sulphoxide was good and excellent optical yields were obtained in favourable cases. 0 Reduction.-Hydrogenation of Carbon- Carbon Multiple Bonds.Hydridic reduction of @-unsaturated carbonyl compounds generally causes reduction of the carbonyl group rather than the double bond but a number of contrary examples have been described this year. Unsaturated esters were reduced by dibaH (Dibal) in the presence of methylcopper( 11) as the catalyst,134 and an alternative strategy using magnesium 127 M. P. Gore and J. C. Vederas J. Org. Chem. 1986,51 3700; D. A. Evans T. C. Britton R. L. Dorow and J. F. Dellaria 1. Am. Chem. Soc. 1986 108 6395 L. A. Trimble and J. C. Vederas J. Am. Chem. SOC.,1986 108 6397. 128 F. A. Davis M. S. Haque T. G. Ulatowski and J. C. Towson J. Org. Chem. 1986 51 2402; F. A. Davies and M. S. Haque J. Org. Chem. 1986 51 4083. 129 D. P. Riley and P.E. Correa J. Chem. SOC.,Chem. Commun. 1986 1097. 130 H. B. Kagan PYlosphoncs Sulfur 1986 27 127. 131 S. Colonna S. Banfi R. Annunziata and L. Casella J. Org. Chv. 1986 51 891. 132 A. Yamagishi J. Chem. SOC.,Chem. Commun. 1986 290. 133 T. Imamoto and H. Koto Chem. Lett. 1986 967. 134 T. Tsuda T. Hayashi H. Satomi T. Kawamoto and T. Saegusa J. Org. Chem. 1986 51 537. 274 P. A. Chuloner in methanol is sufficiently mild that even a sensitive thioacetal group survived (Scheme 73).13' Conjugate reduction by transfer of hydrogen from dimethylphenyl benzimidazoline promoted by aluminium trichloride was found to be suitable for reduction of enones and unsaturated esters but not enal~.'~~ Chloroalkenones could be reduced to a-halogenoketones with modest chemical efficiency but in good optical yield with fermenting Baker's yeast (Scheme 74).137 Reduction of a-alkynyl ketones to truns-enones could be effected with chromium( 11) sulphate or chloride; less than 2% of the cis-isomer could be detected and a number of sensitive functional groups were t~lerated.'~~ n n Reagents Mg MeOH 10°C Scheme 73 82% e.e.syn :anfi = 8.1 1 Reagents Baker's yeast K[H,PO,] [NH4][H2P0,] Ca[C03] Mg[S04] glucose H20 Scheme 74 Hydrogenation ofCurbony1 Compounds. In the past catalytic hydrogenation of enones and enals has been more noted for double bond than for carbonyl reduction. The first catalyst generally capable of promoting the formation of ally1 alcohols has now been reported cis-[H,Ir(PEt,Ph),]'.Selectivities were in the region of 9&96% though the conditions required were fairly severe (30 atm HZ 100 "C,10-22 h).'39 A number of reactions have been added to the armoury of reliable procedures for the selective reduction of aldehydes in the presence of ketones including the use of Na[ BH,]-[Bu4N]Br-CH2C12-H,0'40 and Li[OMe]-HSi(OR)3.141 Reduction of the ester group in (92) (to a primary alcohol) was achieved without epoxide opening using sodium borohydride in ethanol for five minutes followed by rapid quenching with 0.4 molar hydrochloric acid. Under similar conditions one of the 135 I. K. Youn G. H. Yon and C. S. Pak Tetrahedron Left. 1986 27 2409. 136 H. Chikashita and K. Itoh Bull. Chem. SOC.Jpn. 1986 59 1747. 137 M. Utaka S.Konishi and A. Takeda Tetrahedron Lett. 1986 27 4737. A. B. Smith P. A. Levenberg and J. Z. Suits Synthesis 1986 184. 139 E. Farnetti M. Pesce S. KaSpar R. Spogliarich and M. Graziani J. Chern. Soc. Chem. Cornrnun.,1986 746. 140 C. S. Rao A. A. Deshmukh and B. J. Patel Indian J. Chem. Sect. B 1986 25 626. 141 A. Hosomi M. Hayashida S. Kohra and Y. Tominaga J. Chem. SOC.,Chem. Cornrnun. 1986 1411. Synthetic Methods R' nitrile groups in (93) was reduced to the primary amine.I4' Selective reduction of P-ketoesters to P-ketoalcohols was accomplished as shown in Scheme 75; the intermediate is thought to be the en01ate.l~~ Two new reducing agents K[ Ph3BH] and potassium dialkoxymonoalkyl borohy- dride (94) (synthesized from cyclic boronic esters) have shown excellent selectivity for reduction of 2-methylcylohexanone to the less stable cis alcoh01.'~~'~~ K[ Ph3BH] also shows unusual and useful chemoselectivity; cyclohexanone was reduced in the presence of cyclopentanone with 97% selectivity.Reagents i KH THF 0 "C; ii AIH3 THF 25 "C Scheme 75 98% selective Reagent [Me,N][HB(OCOMe),] Scheme 76 Numerous workers continue to report diastereoselective reductions of hydroxy- ketones and their derivatives (for example Scheme 76).'46 This type of P-chelation control is still probably the most popular directing effect but other routes to stereoselection are becoming more widely used. Thus in the stereoselective reduction of a#-dialkoxyketones (95) (Scheme 77) the reaction was a-chelation controlled; Zn[ BH4I2 gave the best re~u1ts.l~~ A highly selective synthesis of 2-alkenyl-l,3-diols 142 J.Mauger and A. Robert J. Chem SOC.,Chem. Commun. 1986 395. 143 K. Isobe K. Mohri H. Sano J. Taga and Y. Tsuda Chem. Pharm.Bull. 1986,34 3029. 144 N. M. Yoon K. E. Kim and J. Kang J. Org. Chem. 1986 51 226. 145 H. C. Brown W. S. Park J. S. Cha B. T. Cho and C. A. Brown J. Org. Chem. 1986 51 337. 146 D. A. Evans and K. T. Chapman Tetrahedron Lett. 1986.27 5939. 147 H. Iida N. Yamazaki and C. Kibayashi J. Org. Chem. 1986 51 3769. P. A. Chaloner OCH20Me OCHZOM i ii iii or iv Bno+R BnO+ Bnos:Me + MeOCH20 MeOCH20 OH MeOCH20 OH (951 64:36->99 1 Reagents i Na[BH,]; ii vitride; iii Zn[BH4],; iv Li[AIH4] Scheme 77 (Scheme 78) used a trimethylsilyl directing group the product being used in the total synthesis of a~enaciolide.'~~ Chiral methyl malates and related systems have been prepared by microbial asymmetric reduction (Scheme 79)'49 but there has been a general trend towards the use of isolated enzyme preparations for reduction.1-Hydroxypropanone was reduced to (R)-1,2-propane diol in 98% optical yield using glycerol dehydrogenase isolated from Enterobacter aerogenes or Cellurnonas sp. these enzymes providing somewhat different specificities from those shown by HLADH or yeast alcohol dehydr0gena~e.l~' Me3%Y Me3Si me351 v Y >99 1 Reagent Li[Et,BH] Scheme 78 H0' HO-syn:anti = 39:61 >99% e.e. Reagents i Cundidu ulbicans; ii BH,.Me,S Na[ BH,]; iii CF,COOH Scheme 79 Other Reductions.Hydrogenolysis of functional groups attached to aryl allyl and alkyl groups has received much wider attention over the last year. The most widely applicable route involves oxidative addition to palladium(o) followed by attack or transfer of hydride. Examples are shown in Scheme 80.'5','52In related procedures K. Suzuki M. Shimazaki and G. Tsuchihashi Tetrahedron Letr. 1986 27 6233. I49 H. Akita H. Matsukura and T. Oishi Chem. Pharm. Bull. 1986 34 2656. 1so L. G. Lee and G. M. Whitesides J. Org. Chem. 1986 51 25. Y. Akita A. Inoue Y. Mori and A. Ohta Heterocycles 1986 24 2093. N. Ono I. Hamamoto A. Kamimura and A. Kaji J. Org. Chem. 1986 51 3734. Synthetic Methods 277 .c 0 Reagents i H, [Pd(PPh,),] K[OCOMe] DMF; ii Na[BH,] [Pd(PPh3),] THF A Scheme 80 propargyl acetates and carbonates have been reduced to allenes with good selectivity (Scheme 81).'53*'54By contrast the deoxygenation of (96) was achieved without isomerization to the allene by protection as a cobalt carbonyl adduct followed by reduction with diborane methyl sulphide and trifluoroacetic acid.'55 Reduction of carbonyl groups to hydrocarbons was accomplished by hydrogenation in the pres- ence of rhodium(r) and /3-~yclodextrin.'~~ Reagents i [Pd2(dba)J [NH4][HC00] THF; ii [Pd(PPh,),] (Me,CH),CHOH SmI Scheme 81 The reductive cleavage of chiral acetals such as (97) may be effected with very high diastereoselectivity (-98 :2) using either dibaH or Et3SiH-TiC1 followed by KF (Scheme 82).The ethers produced were readily cleaved to chiral alcohols using PCC-K2[C03].'57 153 J. Tsuji T. Sugiura M.Yuhara and I. Minami J. Chem. SOC.,Chem. Commun. 1986 922. 154 T. Tabuchi J. Inanaga and M. Yamaguchi Tetrahedron Lett. 1986,21 5237. 15s D. F. McComsey A. B. Reitz C. A. MaryanofT and B. E. Maryanoff Synth. Commun. 1986 16 1535. 156 H. A. Zahalka and H. Alper Organometallics 1986 5 1909. 157 K. Ishihara A. Mori 1. Arai and H. Yamamoto Tetrahedron Lett. 1986 27 983 and 987. 278 P. A. Chaloner +HO OH Ox0 @ Et +y.Et / / BU BU (97) Reagents dibaH -20 "C CH,CI Scheme 82 HO NOCHzPh HO NH2 HO NHz Bu Bu Bu -Bu + BuLBu syn 1 anti = 52:48 96 4 PhCH20 N NHOCH2Ph NHOCHzPh + Ph\OH Ph>OH ph%oCoMe 99 1 Reagents Li[AlH,]; ii PhMe,SiH CF,COOH Scheme 83 Diastereoselective reduction of the 0-benzyl oximes of p-hydroxyketones may be achieved using either Li[AlH4] or PhMe,SiH-CF,COOH (Scheme 83).In the second example the stereoisomeric oxime derivative gave much less successful results reinforcing the thesis that the stereoselection is sterically rather than chelation ~ontrolled.'~~~'~~ Non-redox Conversions.-Substitution at sp3-Hybridized Carbon. The ready availabil- ity of chiral epoxy alcohols by the Sharpless reaction has encouraged studies of their further transformations. Their opening with sodium azide supported on zeolite clay is generally regioselective for attack remote from the hydroxyl group and the reagent is easy to prepare manipulate and separate from the products.'60 Opening with trimethylsilyl azide in the presence of titanium( IV) isopropoxide was rather regioselective for attack on the less-substituted carbon atom of the epoxide.Conversion of epoxides into chlorohydrins with titanium( IV) chloride is stereo- specific and regioselective; it is particularly valuable in that it tolerates acetal protecting groups normally labile to aqueous acid.'62 The problems of esterification and macrolactonization using alkyl halides continue to attract attention. 2,4,6-Trimethylbenzoic acid may be esterified by alkyl halides in the presence of a solid-liquid phase-transfer catalyst such as Aliquat 336. Similar K. Narasaka Y. Ukaji and S.Yamazaki Bull. Chem. SOC.Jpn. 1986 59 525 159 M. Fujita H. Oishi and T. Hiyarna Chem. Lerr. 1986 837. 160 M. Onaka K. Sugita and Y. Izumi Chem. Lett. 1986 1327. 161 D. Sinou and M. Emziane Tetrahedron Lert. 1986 27 4423. 162 C.-L. Spawn G. J. Drtina and D. F. Wiemer Synthesis 1986 315. Synthetic Methods conditions suffice for hydrolysis thus providing a convenient alternative to the strongly acidic media usually associated with reactions of such hindered species.'63 This and numerous other related reactions were also achieved in the presence of the tetraethylammonium salt of pyrrolidone.'64 Dimethylcarbonate has been used as a versatile inexpensive and safe methylating agent for 2-alkylimidazoles thiols and phenols under phase-transfer condition^.'^' Mercury(11) chloride/iodine is a useful reagent for the regiospecific synthesis of a-iodocarbonyl compounds avoiding the use of enol derivatives.'66 The bromina- tion of enantiomerically pure acetals of alkyl aryl ketones is very stereoselective (Scheme 84).The product acetals could be hydrolysed to a-bromoketones by methane sulphonic acid in methanol without ra~emization.'~' MeOOC COOMe MeOOC. ,COOMe MeOOC ,COOMe 90:10-94:6 Reagents Br, HBr CCI, 15 "C Scheme 84 Substitution at sp2-HybridizedCarbon. The halogenation of phenols phenol ethers and aromatic amines may be made extremely regioselective for the 4-isomer using [Me,SCl]+Cl-. The observed selectivity is related to a late arenium ion-like transition state with a bulky halogenating agent.16* 2-Substitution of N-monoalkyl aro- matic amines could be accomplished by the protection lithiation sequence of Scheme 85 which can be performed as a one-pot process.'69 Phenyl ethers and amines cannot be synthesized by the normal Williamson process; the copper-catalysed reactions of organobismuth compounds developed by Barton's group provide a convenient alternative."' Many more examples of the enantioselective formation and hydrolysis of acid derivatives catalysed by enzyme preparations have been reported this year.Some R Reagents i BuLi THF; ii CO,; iii [Me,C]Li THF; vi E+; v HCI H20,0°C; vi A Scheme 85 163 A. Loupy M. Pedoussaut and J. Sansoulet J. Org. Chem. 1986 51 740. 164 T. Shono 0. Ishige H. Uyama and S.Kashimura J. Org. Chem. 1986 51 546. 165 M. Lissel S. Schmidt and B. Neumann Synthesis 1986 382. 166 J. Barluenga J. M. Martinez-Gallo C. Najera and M. Yus Synthesis 1986 678. 167 G. Castaldi S. Cavicchioli C. Giordano and F. Uggeri Angew. Chem. Znt. Ed. Engl. 1986 25 259. 168 G. A. Olah L. Ohannesian and M. Arvanaghi Synthesis 1986 868. 169 A. R. Katritzky W.-Q. Fan and K. Akutagawa Tetrahedron 1986 42 4027. 170 D. H. R. Barton J.-P. Finet. J. Khamsi and C. Pichon Tetrahedron Lett. 1986 27 3615 and 3619. 280 P. A. Chaloner of these involve simple hydrolyses of racemic esters (Scheme 86),'713'72 whilst others are selective hydrolyses of meso diesters giving rise to highly functionalized chiral building blocks and potentially at least allowing conversion of all the material into one enantiomer (Scheme 87).'73As in all other areas of asymmetric synthesis standards are rising and most of the reported enantiomer excesses are greater than 90% crucial to any large scale or commercial application.The use of enzymes in all areas of synthesis has been reviewed.'74 Ph\rCI i_ Phycl Ph + FCl I OH OKPr 0 OKPr 0 t) 30O/O 100% e.e. 43O/O 100% e.e. R'. ,COOH R' .COOMe R' R' 7-52 '/o 3 1-8 1Yo up to 90% e.e. up to 61% e.e. Reagents i Lipoprotein lipase Ammo p Na2[HP04] K[H2P04] pH 7; ii pig-liver esterase Scheme 86 OCH2Ph P hC H 20, I MeCOO OCOMe OH OCOMe THPO OH 95% s Reagents i lipase E.C. 3.1.1.34; ii 4-Me-C,H4S03H DHP 25 "C; iii K2[C03] MeOH Scheme 87 Addition to C-C Multiple Bonds.Asymmetric hydroboration of heterocyclic alkenes with diisopinocampheyl borane (iPC,BH) gives alcohols in up to 100% enantiomer excess. iPCBH2 may generally be used to produce the other enantiomer of a desired alcohol but optical yields are usually 10wer.'~' p-Halogenoalkenyl ketones have been prepared from the corresponding alkynones (Scheme 88). By a change in the conditions both stereoisomers could be obtained with good selectivity and a related compound was used in an approach to 171 H. Kutsuki I. Sawa J. Hasegawa and K. Watanabe Agric. Biol. Chem. 1986 50 2369. 172 S. Ramaswamay R. A. H. F. Hui and J. B. Jones J. Chem. Soc. Chem. Commun. 1986 1545. 173 D. Breitgoff K. Laumen and M. P.Schneider J. Chem. Soc. Chem. Commun. 1986 1523. 174 J. B. Jones Tetrahedron 1986 42 3351. 175 H. C. Brown and J. V. N. V. Prasad J. Am. Chem. Soc. 1986 108 2049. Synthetic Methods 28 1 Reagent i 0Yo 85 O/o 11 65 % 9Yo Reagents i NaI CF,COOH 25 "C; ii NaI MeCOOH 25 "C Scheme 88 pa1yt0xin.l~~ Bromination of alkynes by [Bu,N][ Br,] gave truns-dibromoalkenes with excellent stereoselectivity under particularly mild condition^.'^^ Miscellaneous. Mild and selective methods continue to be sought for the conversion of acetals and thioacetals into carbonyls and routes not requiring aqueous conditions figure prominently. A combination of phenyl dichlorophosphate and sodium iodide may be used at near neutral pH in benzene,'78 whilst iodine in methanol cleaved carbohydrate acetals without the loss of glycosidic bonds.'79 Iron( 111) chloride on silica promotes acetal cleavage much more rapidly than that of triphenylmethyl or t-butyldimethylsilyl ethers and so could be used for selective deprotection of (98).180 The use of bromine in tetrachloromethane or tris(pyridyl)iron(111) perchlorate under acidic conditions provided mild high-yielding and convenient methods for dethioacetalization.'81.'82 (98) (99) w 0 NC' 'NHR (100) (101) Reagents RNH, KCN MeCOOH ultrasound Scheme 89 '76 M.Taniguchi S. Kobayashi M. Nakagawa T. Hino and Y. Kishi Tetrahedron Lett. 1986 27 4759 and 4763. 177 J. Berthelot and M. Fournier Can. J. Chem. 1986 64 603. 178 H.-J. Liu and S. Y. Uu Synth.Commun. 1986 16 1357. 179 W. A. Szarek A. Zamojski K. N. Tiwari and E. R. Ison Tetrahedron Lett. 1986 27 3827. 180 K.S. Kim Y. H. Song €3. H. Lee and C. S. Hahn J. Org. Chem. 1986 51,404. 18' M. Murase E. Kotani and S. Tobinaga Chem. Phann. Bull, 1986 34 3595. 182 R. Caputo G. Ferreri and G. Palumbo Tetrahedron 1986 42 2369. P. A. Chaloner The t-butyldimethylsilyl group has been widely used for the protection of alcohols and the related t-butyldiphenylsilyl function is now reported by Over- man's group to be equally useful in the blocking of primary amino groups. The derivatives RNHSiPh,(CMe,) are stable to chromatography basic hydrolytic alkylating and acylating reagents. They could be smoothly cleaved by dilute acid or ~yridine-HF.'~~ Amines may also be protected with #3-trimethylsilylethane sul- phony1 chloride; (99) was stable to refluxing CF,COOH 6M-HC1 [Bu,N]F BF, and 40% HF being cleaved only by CSF-[BU,N]F.'~~ Two groups have reported the enantioselective synthesis of cyanohydrins.Cataly- sis by the peptide cycle(S-Phe-S-His) was the more successful giving optical yields of up to 82%.lX5In crystalline cyclodextrin complexes up to 33% optical yields were achieved.'86 An intriguing use of ultrasound in this area has been noted; under ultrasonic irradiation (100) was converted into the Strecker product (lOl) whereas without such irradiation only the cyanohydrin was formed (Scheme 89).lg7 183 L. E. Overman M. E. Okazaki and P. Mishra Tetrahedron Lett. 1986 27 4391. 184 S.M. Weinreb D. M. Demko T. A. Lessen and J. P. Demers Tetrahedron Lett. 1986 27 2099. Y. Kobayashi S. Asada I. Watanabe H. Hayashi Y. Motoo and S. Inoue Bull. Chem. SOC.Jpn. 1986 59 893. H. Gountzos W. R. Jackson and K. J. Harrington Aust. J. Chem. 1986 39 1135. 187 J. C. MenCndez G. G. Trigo and M. M. Sollhuber Tetrahedron Lett. 1986 27 3285.